It is common practice in the pharmaceutical industry to use salt forms of drugs, e.g. salts with physiologically acceptable organic or inorganic acids and bases, such as hydrogen chloride, sulphuric acid, maleic acid, ethanolamine, meglumine and the like. For drugs with basic groups, e.g. amine groups, it is feasible to use salts with organic or inorganic acids.
The drug salts are frequently used in preference to the drug itself, for example because of their higher solubility or greater biotolerability.
Many alkaline drug compounds cause irritation of tissue or mucosa. In particular, high local concentration can cause severe irritation and ulceration of the oesophagus. These compounds may also have an unpleasant taste and accordingly they can be administered provided with a polymeric film coating to delay drug release. Such coatings however add to the cost and complexity of formulation.
The present invention is based upon the finding that drug salts with sugar acids exhibit surprising beneficial properties, in particular enhanced uptake and controlled release properties. In particular, insoluble or poorly soluble drug:sugar acid salts have been found to have a drug release profile which is not undesirably dependent on the pH of the surrounding body fluid, eg gastrointestinal fluid.
By the term "sugar acids" is meant herein mono-, di-, oligo- and poly-saccharides (such as xylose, fructose, glucose, sucrose, lactose, maltose, cellobiose, trehalose, sorbitol, mannitol and dextran) which carry oxyacid groups on the saccharide moieties (eg carboxyl groups or esters or oxyacids, such as phosphorus and sulphur oxyacids, with the sugar hydroxyls), which sugar acids, in the case of the polysaccharides (and preferably also the oligosaccharides, disaccharides and monosaccharides), contain a high ratio of acid groups to monosaccharide units, ie at least 2:1, preferably at least 3:1. Such sugar acids have been used in various medicaments but have not previously been proposed for use in forming salts of organic drug compounds.